rs7350355

Positions:

• chrX-153982294-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003492.3(TMEM187):​c.232A>G​(p.Met78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,209,247 control chromosomes in the GnomAD database, including 35,343 homozygotes. There are 101,952 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.35 (6339 hom., 12549 hem., cov: 25)
  • Exomes 𝑓: 0.24 (29004 hom. 89403 hem.)
• Consequence: TMEM187 NM_003492.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

Genes affected

TMEM187 (HGNC:13705): (transmembrane protein 187) This gene consists of two exons and encodes a multi-pass membrane protein. An alternatively spliced transcript variant encoding the same protein has been found, but its biological validity is not determined. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.7919515E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3	c.232A>G	p.Met78Val	missense_variant	2/2	ENST00000369982.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM187	ENST00000369982.5	c.232A>G	p.Met78Val	missense_variant	2/2	1	NM_003492.3	P1
TMEM187	ENST00000425274.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.351 AC: 39582 AN: 112757 Hom.: 6330 Cov.: 25 AF XY: 0.358 AC XY: 12507 AN XY: 34937

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.373

GnomAD3 exomes AF: 0.366 AC: 64874 AN: 177474 Hom.: 10880 AF XY: 0.350 AC XY: 22330 AN XY: 63830

Gnomad AFR exome AF: 0.585

Gnomad AMR exome AF: 0.618

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.725

Gnomad SAS exome AF: 0.575

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.325

GnomAD4 exome AF: 0.238 AC: 260708 AN: 1096434 Hom.: 29004 Cov.: 33 AF XY: 0.247 AC XY: 89403 AN XY: 362302

Gnomad4 AFR exome AF: 0.582

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.726

Gnomad4 SAS exome AF: 0.571

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.298

GnomAD4 genome AF: 0.351 AC: 39636 AN: 112813 Hom.: 6339 Cov.: 25 AF XY: 0.359 AC XY: 12549 AN XY: 35003

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.382

Alfa AF: 0.229 Hom.: 15494

Bravo AF: 0.386

TwinsUK AF: 0.175 AC: 648

ALSPAC AF: 0.173 AC: 501

ESP6500AA AF: 0.561 AC: 2148

ESP6500EA AF: 0.183 AC: 1229

ExAC AF: 0.351 AC: 42616

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-1.0	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.50
DANN	Benign	0.46
DEOGEN2	Benign	0.00072	T
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0000038	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.029
Sift	Benign	0.32	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.012
MPC		0.16
ClinPred		0.0018	T
GERP RS		2.7
Varity_R		0.055
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7350355; hg19: chrX-153247745; COSMIC: COSV64141572; COSMIC: COSV64141572;